Fat Attenuation Index of Renal Cell Carcinoma Reveals Biological Characteristics and Survival Outcome

Hongkai Wang; Yu Wei; Xiaoxin Hu; Jian Pan; Junlong Wu; Beihe Wang; Hailiang Zhang; Guohai Shi; Xiaohang Liu; Jinou Zhao; Yao Zhu; Dingwei Ye

doi:10.3389/fonc.2022.786981

Fat Attenuation Index of Renal Cell Carcinoma Reveals Biological Characteristics and Survival Outcome

Front Oncol. 2022 Jun 9:12:786981. doi: 10.3389/fonc.2022.786981. eCollection 2022.

Authors

Hongkai Wang^{1

2}, Yu Wei^{1

2}, Xiaoxin Hu^{2

3}, Jian Pan^{1

2

4}, Junlong Wu^{1

2}, Beihe Wang^{1

2}, Hailiang Zhang^{1

2}, Guohai Shi^{1

2}, Xiaohang Liu^{1

2}, Jinou Zhao^{1

2}, Yao Zhu^{1

2}, Dingwei Ye^{1

2}

Affiliations

¹ Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Pathology, Fudan University, Shanghai, China.
⁴ Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract

Purpose: The computed tomography fat attenuation index (FAI) is an ideal quantifiable imaging factor to identify the inflammation degree of peri-tumor adipose tissue. We aimed to verify whether FAI could reflect peri-tumor adipose inflammation, predict the survival outcome of renal cell carcinoma (RCC), and discover transcriptomic features of tumor tissues and adjacent adipocytes.

Materials and methods: Two clinical cohorts (Fudan University Shanghai Cancer Center [FUSCC] cohort [n=129] and TCGA cohort [n=218]) were used to explore the association between FAI and clinical outcome. A prospective cohort (n = 19) was used to discover the molecular phenotyping of peri-tumor adipose tissue and tumor tissue according to their FAI value. A clinical cohort (n = 32) in which patients received cyto-reductive surgery was used to reveal the dynamic change of FAI.

Results: A high peri-tumor FAI was significantly associated with a worse outcome in both the FUSCC (HR = 2.28, p = 0.01) and the TCGA cohort (HR = 2.24, p <0.001). The analysis of the RNA expression of paired RCC tissue and peri-tumor fat tissue showed synchronized alterations in pathways such as cytokine-cytokine receptor interaction and complement and coagulation cascades. RCC tissues showed significant alterations in the neuroactive ligand-receptor interaction pathway. Immune deconvolution analysis showed enhanced infiltration of macrophages in high FAI tumor tissues with a lower angiogenesis level. We also observed synchronous dynamic changes in FAI and tumor size after targeted therapy.

Conclusion: In summary, FAI could be used in RCC to reflect the biological characteristics and tumor immune micro-environment of both the tumor and the peri-tumor adipose. High peri-tumor FAI had the potential to predict a worse survival outcome in various cohorts. This study demonstrates that the crosstalk exists between a tumor and its micro-environment and could be reflected easily by imaging procedures, which could facilitate clinical decision making.

Keywords: CT fat attenuation index; adipocyte; immune micro-environment; obesity paradox; renal cell carcinoma.